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Interferon regulatory factor 8 (IRF8) interacts with the B cell lymphoma 6 (BCL6) corepressor BCOR

Jeongheon Yoon1, Xianxum Feng1, Yong-Soo Kim1

  • 1From the Laboratory of Immunogenetics, NIAID, National Institutes of Health, Rockville, Maryland 20852 and.

The Journal of Biological Chemistry
|October 22, 2014
PubMed

Insights

Interferon regulatory factor 8 (IRF8) interacts with B cell lymphoma 6 (BCL6) corepressor (BCOR) and BCL6. IRF8 regulates Bcor and Bcl6 transcription, suggesting a BCOR-BCL6-IRF8 complex in germinal center B cell function.

Area of Science:

  • Immunology
  • Molecular Biology
  • Transcriptional Regulation

Background:

  • B cell lymphoma 6 (BCL6) corepressor (BCOR) is known to interact with BCL6.
  • Interferon regulatory factor 8 (IRF8) targets genes in germinal center B cells, including BCL6.
  • The role of BCOR in normal B cell development and function requires further investigation.

Purpose of the Study:

  • To identify novel binding partners of IRF8.
  • To elucidate the interaction between IRF8, BCOR, and BCL6.
  • To understand the functional consequences of these interactions in B cells.

Main Methods:

  • Retrovirus-based protein complementation assay screening in mouse pre-B cells.
  • Identification of interacting protein domains.
  • siRNA-mediated IRF8 knockdown in a mouse B cell lymphoma cell line.

Main Results:

  • IRF8 directly interacts with BCOR, requiring specific domains on both proteins.
  • IRF8 also directly interacts with BCL6.
  • IRF8 knockdown represses Bcor transcription and enhances Bcl6 transcription.

Conclusions:

  • A BCOR-BCL6-IRF8 complex is proposed to modulate BCL6-associated transcriptional regulation.
  • This complex plays a role in germinal center B cell function.
  • IRF8 is identified as a novel interacting partner of BCOR and BCL6.

Keywords:
Gene ExpressionImmunologyLymphocyteProtein ComplexProtein-Protein InteractionTranscription Repressor

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